Lou, Peng; Liu, Shuyun; Wang, Yizhuo; Pan, Cheng; Xu, Xuewen; Zhao, Meng; Liao, Guangneng; Yang, Guang; Yuan, Yujia; Li, Lan

DOI: PMID:

Abstract

Chronic wounds remain a worldwide clinical challenge, and bioactive materials that can promote skin regeneration are required. Self-assembling peptide (SAP) hydrogels have shown great potential in tissue repair, but their regenerative efficacy and possible mechanism in chronic wound healing are unclear. Here, we report an SAP (KGH) that enhances extracellular matrix (ECM) remodeling and angiogenesis, thereby promoting chronic wound healing in diabetic mice. In vivo, the KGH hydrogel was retained in wounds up to 7 days after injection, and it was effective in speeding up wound closure by ∼20% compared to the control groups and enhancing angiogenesis (e.g., VEGFA, CD31+ capillaries), cell proliferation (e.g., PCNA+ cells), formation of granulation tissue (e.g., α-SMA), and ECM deposition/remodeling (e.g., collagen I, fibronectin). In vitro, the KGH hydrogel created a 3D microenvironment for skin cells, maintained the sustained growth of cell spheroids, and increased the secretion of ECM proteins (e.g., laminin) and growth factors (e.g., PDGFB, VEGFA, and TGF-β) in skin keratinocytes compared to the conventional 2D culture. Mechanistically, the KGH hydrogel might promote wound tissue regeneration by activating the Rho/ROCK and TGF-β/MEK/MAPK pathways. As a type of designed material, SAP can be further re-engineered with biological motifs, therapeutic reagents, or stem cells to enhance skin regeneration. This study highlights that SAP hydrogels are a promising material platform for advanced chronic wound healing and might have translational potential in future clinical applications.

Keywords

Chronic wound ; Self-assembling peptide ; 3D culture ; Extracellular matrix ; Angiogenesis

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